Appraisal of the Possible Role of PPAR gamma Upregulation by CLA of Probiotic Pediococcus pentosaceus GS4 in Colon Cancer Mitigation

The prevalence of colon cancer (CC) is increasing at the endemic scale, which is accompanied by subsequent morbidity and mortality. Although there have been noteworthy achievements in the therapeutic strategies in recent years, the treatment of patients with CC remains a formidable task. The current study focused on to study role of biohydrogenation-derived conjugated linoleic acid (CLA) of probiotic Pediococcus pentosaceus GS4 (CLA(GS4)) against CC, which induced peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in human CC HCT-116 cells. Pre-treatment with PPAR gamma antagonist bisphenol A diglycidyl ether has significantly reduced the inhibitory efficacy of enhanced cell viability of HCT-116 cells, suggesting the PPAR gamma-dependent cell death. The cancer cells treated with CLA/CLA(GS4) demonstrated the reduced level of Prostaglandin E2 PGE(2) in association with reduced COX-2 and 5-LOX expressions. Moreover, these consequences were found to be associated with PPAR gamma-dependent. Furthermore, delineation of mitochondrial dependent apoptosis with the help of molecular docking LigPlot analysis showed that CLA can bind with hexokinase-II (hHK-II) (highly expressed in cancer cells) and that this association underlies voltage dependent anionic channel to open, thereby causing mitochondrial membrane depolarization, a condition that initiates intrinsic apoptotic events. Apoptosis was further confirmed by annexin V staining and elevation of caspase 1p10 expression. Taken all together, it is deduced that, mechanistically, the upregulation of PPAR gamma by CLA(GS4) of P. pentosaceus GS4 can alter cancer cell metabolism in association with triggering apoptosis in CC.